Gregor’s Genome

What do you get the man who discovered the fundamental laws of inheritance and who’s also been dead for 138 years for his 200th birthday?

How about a big party and a sequenced genome!

Gregor Mendel was born on July 20, 1822. He grew up on his family’s farm on the border of the Austrian Empire. As a young man, he decided to join the Order of Saint Augustine and become a monk, primarily because it allowed him to continue his education. He then studied, taught, and conducted research in the areas of biology, meteorology, mathematics, and physics before becoming the abbot of St. Thomas Abbey in Brno. A true renaissance man!

Mendel is known as the father of modern genetics because of his famous pea plant experiment. This experiment took place in St. Thomas’ five-acre research garden over 7 years. During this time Mendel meticulously crossed bred and monitored the key physical traits (height, pod shape, pod color, seed shape, seed color, flower position, flower color) of ~ 30,000 pea plants!

The results of this pea plant experiment led Mendel to postulate the idea of hereditary units which he called “factors” and which we now know as genes as well as the “dominant” and “recessive” nature of these factors. Thanks to the peas he also formulated three rules – the law of dominance and uniformity, the law of segregation, and the law of independent assortment. These Mendelian laws are fundamental to our understanding of DNA and inheritance but were also way ahead of their time. They remained largely ignored until the 1900s when they were rediscovered and helped kick-start the modern field of genetics.

Dr. Sarka Pospisilova, a medical geneticist and the vice-rector for research at Masaryk University in Brno, was well acquainted with this history. When she was tasked to commemorate Mendel’s 200th birthday in Brno she gathered together a group of colleagues and friends and they started brainstorming ways to celebrate this influential and inspiring scientist.

One of the craziest ideas? Sequence his genome!

However, when they came back to it the sequencing idea didn’t seem so crazy. Biotechnologies that allow researchers to reconstruct old and even ancient DNA have made incredible progress over the last few years (read more about that here.) It would be possible! However, they also had to ask themselves if this is what Mendel would have wanted. Given his driving desire to examine everything scientifically, including a dying request that an autopsy be performed after his death, they guessed that yes, he would. Next, they consulted the Augustine monks of Prague and Rome. Was this an idea – which would involve excavating a shared grave in the monastery – a plan they could support? The bishops answered yes. Finally, they recruited the help of geneticists who specialized in respectfully and accurately examining DNA in human remains.

The next challenge? Mendel was buried in a group grave. To identify which skeleton was his the researchers work with the local museum to find a known Mendel DNA sample. They swabbed microscopes and glasses, searched through papers, and flipped through personal books and journals. Finally, in an astronomy book, they found a stray hair. By sequencing the mtDNA in the hair and comparing it to mtDNA samples from the unidentified skeletons they were able to find a match. From this skeleton, they took a small tooth sample and were able to extract highly intact “Mendelian” DNA.

Finally, using next-generation sequencing technologies and cutting-edge bioinformatic pipelines, the researchers were able to reconstruct 91% of Mendel’s genome and 99% of the exome with an average coverage of 9.26. With these ~3.2 billion bp they could then search for genetic variants that could give new insights into this famous founder. One of the most interesting was a genetic variant linked to epilepsy and other neurological issues which may explain the periodic nervous breakdowns that Mendel experienced. The full findings were presented as part of the Mendel 2022 conference this past summer and were also published in this book.